Folic acid deficiency, a major cause of nutritional anemia, is a common form of vitamin malnutrition. The goal of this research is to continue an investigation of mechanisms of folate absorption and utilization and to evaluate mechanisms of folate deficiency in pregnant women, in patients with intestinal disease, in alcoholics, in malignancy and in patients on drugs. The technology to be used will depend on chemical and biological synthesis of radioactive and deuterium labeled mono glutamyl and polyglutamyl folates by techniques developed in this laboratory. Quantitative tests of folate absorption in patients with disease will be based on urinary excretion techniques previously reported. Stable isotope (deuterium) labeled folates will be utilized for studies of folate absorption and utilization in pregnancy and in children where the use of radioisotope labeled study compounds is inappropriate or contraindicated. Deuterium labeled folates will aid in the determination of folate pool size and turnover in additon to providing data on absorption. Analysis of the enzymology of folate utilization will depend on enzyme purification techniques including affinity chromatography and conventional methods with chromatographic identification and kinetic analysis of product appearance. Effects of disease and drugs on intestinal deconjugation of polyglutamyl folates will be studied in vivo using labeled synthetic folates and in vitro using preparations of enzymes from intestinal mucosa. Folate binding proteins, isolated from transporting tissues such as intestine and kidney, will be utilized as models for study of folate/membrane/drug interactions. BIBLIOGRAPHIC REFERENCES: Rosenberg, I.H., Solomons, N.W. and Schneider, R.: Malabsorption associated with diarrhea and intestinal infections. Proceed. of Workshop on Impact of Infection on Nutritional Status, Ed.: Wm. Beisel, 1977, in press. Rosenberg, I.H.: Role of Intestinal Conjugase in the Control of the Absorption of Polyglutamyl Folates, in Folic Acid: Biochemistry & Physiology in Relation to the Human Nutrition Requirement, Nat. Acad. Science, pg. 136-146. (Proceed. of a Workshop on Human Folate Requirements), Wash. DC, 1977.